Composition capable of clearing heat and relieving cough as well as preparation method and application of composition

Abstract

The invention discloses a Qingxuan cough-relieving composition as well as a preparation method and application thereof, and relates to the field of traditional Chinese medicine preparations. The preparation method comprises the following steps: (1) distilling mint, fructus aurantii and pericarpium citri reticulatae to obtain volatile oil; (2) soaking radix paeoniae alba in water, continuously performing water extraction on the radix paeoniae alba, folium mori, fried semen armeniacae amarae, radix platycodonis, radix asteris, radix glycyrrhizae and dregs obtained after distillation in the step (1), performing solid-liquid separation, concentrating and drying filtrate, and crushing to obtain extract powder; (3) mixing the extract powder with cane sugar and dextrin, granulating, screening and granulating to obtain granules after granule selection and fine powder passing through a screen; (4) mixing and stirring beta-cyclodextrin and the fine powder, adding the volatile oil, stirring again, discharging and sieving to obtain an inclusion compound; and (5) mixing the clathrate compound with the particles to obtain the product. The content of albiflorin and hesperidin in the prepared composition for clearing and relieving cough is higher, the stability is better, the preparation method is simple and convenient, the production cost is low, and the composition is suitable for industrial production and application.

Description

Technical Field

[0001] The present invention relates to the field of traditional Chinese medicine preparations, and in particular to a cough-clearing and antitussive composition and a preparation method and application thereof. Background Art

[0002] Cough is a common lung disease in children. Children's coughs are generally divided into exogenous and internal injuries. Physiologically, the lung is a delicate organ that cannot tolerate the invasion of cold, heat, dryness, dampness and other evils. It is connected to the nasal cavity and the skin. It is clear in nature, responsible for the release of qi and descending, and responsible for breathing. However, the lungs of children are more delicate, with sparse barriers, weak defenses, and often unable to adjust to cold and heat. They are easily invaded by external evils. In addition, children have a pure yang body, and evils are easy to turn into heat. Therefore, in clinical practice, children's coughs caused by exogenous factors are more common than those caused by internal injuries. At present, Western medicine often uses antiviral drugs for clinical treatment, but the effect is general, and repeated use of drugs or increased dosages are prone to adverse reactions.

[0003] Traditional Chinese medicine has unique advantages. Professor Zhang Zhenyu developed Qingxuan cough-relieving granules based on folk prescriptions. They are composed of mulberry leaves (Latin name Folium Mori), mint (Latin name Mentha hyplocalyx Briq.), stir-fried bitter almonds (Latin name Semen Armeniacae Amarum.), platycodon (Latin name Platycodon grandiflorus (Jacq.) A.DC.), white peony root (Latin name Radix Paeoniae Alba), bitter orange peel (Latin name Citrus aurantium L.), tangerine peel (Latin name Pericarpium Citri Reticulatae), aster (Latin name Aster tataricus L.f.), licorice (Latin name Radix The formula is composed of nine herbs, including mulberry leaves, which are sweet and bitter and cool, peppermint, which are pungent and cool, and dispel wind and heat, as the main herbs; apricot kernel and bitter and descending, platycodon, which are pungent and dispersing, and relieve cough and stop phlegm, as the assistant herbs; aster, which is bitter and warm but not hot, white peony, which is sour and restrains yin, and tangerine peel, which is bitter and warm, relieves stagnation and resolves phlegm, as the adjuvant herbs; and liquorice, which harmonizes the herbs, as the guiding herbs. It has the effects of dispelling wind and heat, clearing lungs and stopping coughs, and the prescription combination has no toxic side effects and does not affect the growth and development of children.

[0004] CN1546085A discloses a pharmaceutical composition for treating exogenous wind-heat cough and a preparation method thereof, wherein the pharmaceutical composition is mainly composed of mulberry leaf, mint, bitter almond, platycodon, white peony root, fructus aurantii, aster, dried orange peel and liquorice, and mainly clears and promotes lung qi, and supplemented by descending lung qi, and has antitussive, expectorant and anti-inflammatory effects. However, in the preparation process of the invention, the amount of volatile oil used for inclusion with β-cyclodextrin is large, which increases the production cost, and the inclusion effect and preparation stability are average.

[0005] Therefore, the present invention aims to provide a method for preparing a clear and antitussive composition by improving the process, which reduces production costs, improves raw material utilization, and improves preparation stability. Summary of the invention

[0006] In order to solve the above problems, the present invention provides a clearing and relieving cough composition and a preparation method and application thereof. The preparation method of the present invention reduces production costs, improves the utilization rate of raw materials, and also improves the stability of the preparation.

[0007] To achieve the above-mentioned object of the invention, the technical solution of the present invention is as follows:

[0008] In a first aspect, the present invention provides a method for preparing a cough-clearing and cough-relieving composition, comprising the following steps:

[0009] (1) steam distilling peppermint, fructus aurantii, and tangerine peel to obtain volatile oil;

[0010] (2) soaking white peony root in water, and continuing to extract with mulberry leaf, fried bitter almond, platycodon, aster, liquorice and the residue after distillation in step (1), separating the solid and liquid, concentrating and drying the filtrate, and crushing to obtain extract powder;

[0011] (3) mixing the extract powder with sucrose and dextrin, granulating, screening and granulating to obtain the selected granules and the fine powder passing through the sieve;

[0012] (4) mixing β-cyclodextrin and the fine powder obtained in step (3) and stirring, adding the volatile oil obtained in step (1) and stirring again, and sieving the discharged material to obtain an inclusion compound;

[0013] (5) Mixing the inclusion compound obtained in step (4) and the selected particles obtained in step (3) to obtain.

[0014] In some embodiments, in step (1), the mass of water added is 1.2-12 times the mass of mint, fructus aurantii, and tangerine peel, preferably 1.6-8 times, and more preferably 2-4 times.

[0015] In some embodiments, in step (2), the mass of water added is 4.8-24 times, preferably 6.4-16 times, and more preferably 8-12 times, of the total mass of white peony root, mulberry leaf, stir-fried bitter almond, platycodon, aster, licorice and the distilled medicinal residue.

[0016] In some preferred embodiments, in step (2), the water extraction is performed 1-3 times, preferably 2 times; the water extraction time is 0.6-3h, preferably 0.8-2h, and more preferably 1h.

[0017] In some preferred embodiments, in step (2), the solid-liquid separation is centrifugation or filtration; preferably filtration.

[0018] In some preferred embodiments, in step (2), the concentration is concentrated under reduced pressure to a relative density of 1.30-1.35.

[0019] In some preferred embodiments, in step (2), the concentration is performed 1-3 times, preferably 2 times;

[0020] In some preferred embodiments, when the number of reduced pressure concentration is 2 times, the first concentration is to a relative density of 1.0-1.45, preferably 1.05-1.30, more preferably 1.10-1.15, and further preferably 1.03-1.09.

[0021] In some embodiments, the amount of sucrose and dextrin used in step (3) is 1.5-3 times the mass of the extract powder, preferably 1.8-3 times, more preferably 2-3 times, and more preferably 2.3-2.75 times.

[0022] In some preferred embodiments, the mass ratio of sucrose to dextrin is 1-3:1; preferably 1.5-2.5:1; and more preferably 2:1.

[0023] In some embodiments, the mass ratio of the volatile oil to β-cyclodextrin in step (4) is 1:0.6-1.4, preferably 1:0.8-1.2; the mass ratio of the volatile oil to the fine powder obtained in step (4) is 1.2-54, preferably 1:1.6-18, and further preferably 1:2-6.

[0024] In some preferred embodiments, after the granulation in step (3), drying is further included, and the drying is: drying at 60-120°C for 3-20 min; preferably drying at 60-100°C for 5-15 min; more preferably drying at 65-95°C for 5-15 min.

[0025] In some preferred embodiments, the screen used for particle selection is a vibrating screen with a double-layer screen.

[0026] In some preferred embodiments, the mixing and stirring time in step (4) is 1.6-32 min, preferably 2.4-16 min, and more preferably 2-6 min; the re-stirring time is 1.2-6 min, preferably 1.6-4 min, and more preferably 2 min.

[0027] In some preferred embodiments, in step (5), the mixing is as follows: the inclusion complex and the selected particles are sucked into a total mixing barrel for 1-5 times, preferably 2-4 times; the mixing speed is 2-50 rpm, preferably 3-20 rpm, and more preferably 4-12 rpm; the mixing time is 6-90 min, preferably 8-60 min, and more preferably 10-30 min.

[0028] In some preferred embodiments, the preparation method comprises the following steps:

[0029] (1) steam distilling peppermint, fructus aurantii, and tangerine peel to obtain volatile oil;

[0030] (2) soaking white peony root in water, combining with mulberry leaf, fried bitter almond, platycodon grandiflorum, aster and liquorice, and continuing water extraction with the residue after distillation in step (1), separating the solid and liquid, concentrating and drying the filtrate, and crushing to obtain extract powder;

[0031] (3) crushing sucrose and the extract powder obtained in (2), mixing the extract powder with sucrose and dextrin, adding ethanol, stirring, granulating to obtain wet granules, drying, cooling, discharging, screening and granulating to obtain selected granules and fine powder passing through a sieve;

[0032] (4) mixing β-cyclodextrin and the fine powder obtained in step (3) and stirring, adding the volatile oil obtained in step (1) and stirring again, and sieving the discharged material to obtain an inclusion compound;

[0033] (5) Mixing the inclusion compound obtained in step (4) and the selected particles obtained in step (3) to obtain.

[0034] Preferably, the ethanol in step (3) is added 1-3 times, preferably 2 times; when the ethanol is added 2 times, the concentration of the first ethanol addition is 95 v / v%, and the mass of the added ethanol is 5-15% of the total weight of the extract powder, sucrose and dextrin; preferably 6-12%; more preferably 6.5-10%; the concentration of the second ethanol addition is 25%-75%, preferably 30%-70%, more preferably 44%-65%; the mass of the second ethanol added is 6-10% of the total weight of the extract powder, sucrose and dextrin; preferably 6-8%; more preferably 6.5-8%; more preferably 7.3%-7.9%.

[0035] In a second aspect, the present invention also provides a method for preparing a cough-clearing composition, comprising the following steps:

[0036] (1) Add 3 times the amount of water to mint, fructus aurantii, and tangerine peel, and distill to extract volatile oil;

[0037] (2) soaking white peony root in water for 3-5 hours, and combining with mulberry leaf, fried bitter almond, platycodon, aster, and licorice. The residue after volatile oil extraction in step (1) is soaked in 6-12 times amount of water for 30 minutes, decocted twice, each time for 1 hour, and the decoction is filtered to obtain a first extract and the residue, adding 6-12 times amount of water to the residue, decocting twice, each time for 1 hour, and filtering the decoction to obtain a second extract, combining the two extracts, concentrating and drying to obtain an extract powder;

[0038] (3) crushing sucrose, mixing it with dextrin and extract powder, adding ethanol with a volume fraction of 95%, stirring evenly, and then adding ethanol with a volume fraction of 55% and stirring again to make wet granules, drying, cooling, discharging, screening granules with 14 mesh / 60 mesh, and refining granules that do not pass 14 mesh with 12 mesh and then selecting granules to obtain selected granules and fine powders that pass through the sieve; the granules are selected using a double-layer sieve, with the upper layer being a 14-mesh sieve and the lower layer being a 60-mesh sieve; the granules are screened to obtain selected granules and fine powders that pass through the sieve;

[0039] (4) sequentially mixing 0.8-1.2 times the amount of β-cyclodextrin as the volatile oil and 2-6 times the amount of the fine powder obtained in step (4) and stirring, adding the volatile oil obtained in step (1), stirring, and sieving the discharged material to obtain an inclusion compound;

[0040] (5) The inclusion compound obtained in step (4) and the selected granules obtained in step (3) are mixed to obtain a cough-clearing and cough-relieving composition.

[0041] In a third aspect, the present invention also provides a cough-clearing and cough-relieving composition prepared according to the above method.

[0042] In some embodiments, the Qingxuan cough-relieving composition, by weight, comprises 108 parts of mint, 54-162 parts of Citrus aurantium, 72-216 parts of dried tangerine peel, 72-216 parts of white peony root, 108-324 parts of mulberry leaf, 54-162 parts of stir-fried bitter almond, 72-216 parts of Platycodon grandiflorum, 72-216 parts of Aster tataricus and 54-162 parts of licorice; preferably 108 parts of mint, 108 parts of Citrus aurantium, 144 parts of dried tangerine peel, 144 parts of white peony root, 216 parts of mulberry leaf, 108 parts of stir-fried bitter almond, 144 parts of Platycodon grandiflorum, 144 parts of Aster tataricus and 108 parts of licorice.

[0043] In a fourth aspect, the present invention also provides the use of the above-mentioned Qingxuan Antitussive Composition in the preparation of a medicine for treating exogenous wind-heat cough.

[0044] In the last aspect, the present invention also provides a qingxuan zhike medicine, which is prepared by the aforementioned preparation method or the aforementioned qingxuan zhike composition.

[0045] In some embodiments, the Qingxuan cough-relieving composition, by weight, comprises 108 parts of mint, 54-162 parts of Citrus aurantium, 72-216 parts of dried tangerine peel, 72-216 parts of white peony root, 108-324 parts of mulberry leaf, 54-162 parts of stir-fried bitter almond, 72-216 parts of Platycodon grandiflorum, 72-216 parts of Aster tataricus and 54-162 parts of licorice; preferably 108 parts of mint, 108 parts of Citrus aurantium, 144 parts of dried tangerine peel, 144 parts of white peony root, 216 parts of mulberry leaf, 108 parts of stir-fried bitter almond, 144 parts of Platycodon grandiflorum, 144 parts of Aster tataricus and 108 parts of licorice.

[0046] In some embodiments, the dosage form of the antitussive drug is granules, tablets or capsules.

[0047] Compared with the prior art, the present invention has the following beneficial effects:

[0048] (1) The antitussive and cough-relieving composition produced by the present invention has better stability.

[0049] (2) The contents of white paeony glycosides and hesperidin in the cough-clearing and cough-relieving composition of the present invention are higher.

[0050] (3) The amount of β-cyclodextrin used in the present invention is small, thereby reducing production costs.

[0051] (4) The method of the present invention is simple, has low production cost, and is suitable for industrial production application. DETAILED DESCRIPTION

[0052] In the following examples, all Chinese medicinal materials were purchased from Anhui Shengantang Pharmaceutical Co., Ltd. The times mentioned in the present invention are relative to the weight of the materials to be processed, for example, "108 kg of mint, 108 kg of Citrus aurantium, and 144 kg of dried tangerine peel are added with 3 times the weight of water", wherein the 3 times weight of water is 3 times the total weight of "mint, Citrus aurantium, and dried tangerine peel";

[0053] The "fine powder obtained in step (3) with 1 times the amount of β-cyclodextrin and 4 times the amount of volatile oil" refers to 1 times the mass of the volatile oil, and 4 times the amount refers to 1 times the weight of the volatile oil.

[0054] The mass of the medicinal residue is calculated based on the mass of the Chinese medicinal raw materials before extraction, such as "144 kg of white peony root is soaked in water for 4 hours, combined with 216 kg of mulberry leaves, 108 kg of fried bitter almonds, 144 kg of platycodon, 144 kg of aster and 108 kg of liquorice, and the medicinal residue after volatile oil extraction in step (1) is soaked in 10 times the amount of water for 30 minutes" The mass of the "medicinal residue" is the total mass of "mint, fructus aurantii and tangerine peel" before distillation.

[0055] The amount of water used for soaking in the present invention is enough to soak 2-5 cm of the medicinal material surface.

[0056] In the step (3) of the present invention, the "granules after granulation" are the sieve under the 14-mesh sieve and the sieve over the 60-mesh sieve, and the "fine powder passing through the sieve" are the sieve under the 60-mesh sieve.

[0057] Unless otherwise specified, all percentages in the present invention are by volume.

[0058] Example 1 Preparation method of the Qingxuan cough-relieving composition

[0059] (1) Add 3 times the amount of water to 108 kg of mint, 108 kg of fructus aurantii, and 144 kg of dried orange peel, and distill to extract 2.26 kg of volatile oil;

[0060] (2) 144 kg of white peony root is soaked in water for 4 hours, and then combined with 216 kg of mulberry leaf, 108 kg of fried bitter almond, 144 kg of platycodon, 144 kg of aster and 108 kg of liquorice. The residue after the volatile oil extraction in step (1) is soaked in 10 times the amount of water for 30 minutes, and decocted twice, each time for 1 hour. The decoction is filtered through an 80-mesh sieve at the bottom of the tank, and the filtrate released is the first extract; the filtered residue is added with 8 times the amount of water again, and the same operation is performed, and the filtrate obtained is the second extract; the two extracts are combined and concentrated to a relative density of 1.03-1.09 (measured at 50° C.), and then passed through a 300-mesh sieve while hot, and further concentrated under reduced pressure to a relative density of 1.15-1.20 (measured at 50° C.), and then filtered through a 300-mesh sieve while hot to obtain an extract; the obtained extract is dried using a vacuum dryer to obtain 360 kg of extract powder;

[0061] (3) Sucrose is crushed through 80 mesh; 560 kg of sucrose powder, 280 kg of dextrin, and 360 kg of extract powder are sucked into a wet mixing granulator, and after mixing, 100 kg of 95% ethanol is added, and after stirring evenly, 91 kg of 55% ethanol is added and stirred; the soft material is sieved through a 20-mesh sieve for granulation; the wet granules are sucked into a boiling dryer, and when the material temperature reaches 75°C, the drying is continued for 15 minutes, the heating is stopped, and the temperature is lowered. When the material temperature reaches below 50°C, the material is discharged; the dried granules are selected, and the selection screen mesh number is 14 mesh / 60 mesh, and the selected granules and fine powder passing through the screen are obtained;

[0062] (4) adding β-cyclodextrin in an amount of 1 times that of volatile oil and the fine powder obtained in step (3) in an amount of 4 times that of volatile oil into a high-efficiency mixing granulator, stirring for 4 minutes, pouring in the volatile oil obtained in step (1), stirring for 2 minutes, and passing the discharged material through a 14-mesh sieve to obtain an inclusion compound;

[0063] (5) The inclusion compound obtained in step (4) and the selected granules obtained in step (3) are aspirated into a 3000 L total mixing barrel three times, with each aspirating amount being 1 / 3 of the inclusion compound and 1 / 3 of the granules. After the aspiration is completed, the speed of the fixed hopper mixer is set to 8 rpm and mixed for 20 minutes to obtain a clear and antitussive composition.

[0064] Example 2 Preparation method of the Qingxuan cough-relieving composition

[0065] (1) Add 2 times the amount of water to 108 kg of mint, 108 kg of fructus aurantii, and 144 kg of dried orange peel, and distill to extract 1.84 kg of volatile oil;

[0066] (2) 144 kg of white peony root is soaked in water for 3 hours, and then combined with 216 kg of mulberry leaves, 108 kg of fried bitter almonds, 144 kg of platycodon, 144 kg of aster, and 108 kg of liquorice. The residue after the volatile oil extraction in step (1) is soaked in 8 times the amount of water for 10 minutes, and decocted twice, each time for 1 hour. The decoction is filtered through a 100-mesh sieve at the bottom of the tank, and the filtrate released is the first extract; 6 times the amount of water is added to the filtered residue, and the same operation is performed, and the filtrate obtained is the second extract; the two extracts are combined and concentrated to a relative density of 1.03-1.09 (measured at 50° C.), and then passed through a 270-mesh sieve while hot, and further concentrated under reduced pressure to a relative density of 1.05-1.15 (measured at 50° C.), and then filtered through a 270-mesh sieve while hot to obtain an extract; the obtained extract is dried using a vacuum dryer to obtain 300 kg of extract powder;

[0067] (3) crushing sucrose through 80 mesh; sucking 600 kg of sucrose powder, 300 kg of dextrin, and 300 kg of extract powder into a wet mixing granulator, adding 80 kg of 95% ethanol after mixing, stirring evenly, and then adding 88 kg of 44% ethanol and stirring; the soft material is sieved through a 20-mesh sieve for granulation; the wet granules are sucked into a boiling dryer, and when the material temperature reaches 75°C, continue drying for 10 minutes, stop heating, start cooling, and discharge the material when the material temperature reaches below 50°C; select the dried granules, and select the granules with a sieve mesh of 12 mesh / 50 mesh to obtain the selected granules and the fine powder passing through the sieve;

[0068] (4) adding 1.2 times the amount of β-cyclodextrin as the volatile oil and 2 times the amount of the volatile oil as the fine powder obtained in step (3) to a high-efficiency mixing granulator, stirring for 4 minutes, pouring in the volatile oil obtained in step (1), stirring for 2 minutes, and passing the discharged material through a 12-mesh sieve to obtain an inclusion compound;

[0069] (5) The inclusion compound obtained in step (4) and the selected granules obtained in step (3) are aspirated into a 3000 L total mixing barrel three times, with each aspirating amount being 1 / 3 of the inclusion compound and 1 / 3 of the granules. After the aspiration is completed, the speed of the fixed hopper mixer is set to 4 rpm and mixed for 20 minutes to obtain a clear and antitussive composition.

[0070] Example 3 Preparation method of the Qingxuan cough-relieving composition

[0071] (1) Add 4 times the amount of water to 108 kg of mint, 108 kg of fructus aurantii, and 144 kg of dried orange peel, and distill to extract 1.12 kg of volatile oil;

[0072] (2) 144 kg of white peony root is soaked in water for 5 hours, and then combined with 216 kg of mulberry leaf, 108 kg of fried bitter almond, 144 kg of platycodon, 144 kg of aster and 108 kg of liquorice. The residue after the volatile oil extraction in step (1) is soaked in 12 times the amount of water for 50 minutes, and decocted twice, each time for 1 hour. The decoction is filtered through a 60-mesh sieve at the bottom of the tank, and the filtrate released is the first extract; 12 times the amount of water is added to the filtered residue again, and the same operation is performed, and the filtrate obtained is the second extract; the two extracts are combined and concentrated to a relative density of 1.03-1.09 (measured at 50° C.), and then passed through a 325-mesh sieve while hot, and then continued to be concentrated under reduced pressure to a relative density of 1.10-1.20 (measured at 50° C.), and then filtered through a 325-mesh sieve while hot to obtain an extract; the obtained extract is dried using a vacuum dryer to obtain 321 kg of extract powder;

[0073] (3) crushing sucrose through 80 mesh; sucking 586 kg of sucrose powder, 293 kg of dextrin, and 321 kg of extract powder into a wet mixing granulator, adding 120 kg of 95% ethanol after mixing, stirring evenly, and then adding 94 kg of 65% ethanol and stirring; the soft material is sieved through a 20-mesh sieve for granulation; the wet granules are sucked into a boiling dryer, and when the material temperature reaches 75°C, continue drying for 20 minutes, stop heating, start cooling, and discharge the material when the material temperature reaches below 50°C; select the dried granules, and select the granules with a sieve mesh of 16 mesh / 70 mesh to obtain the selected granules and fine powder passing through the sieve;

[0074] (4) adding 0.8 times the amount of β-cyclodextrin as the volatile oil and 6 times the amount of the volatile oil as the fine powder obtained in step (3) to a high-efficiency mixing granulator, stirring for 6 minutes, pouring in the volatile oil obtained in step (1), stirring for 2 minutes, and passing the discharged material through a 16-mesh sieve to obtain an inclusion compound;

[0075] (5) The inclusion compound obtained in step (4) and the selected granules obtained in step (3) are aspirated into a 3000 L total mixing barrel three times, with each aspirating amount being 1 / 3 of the inclusion compound and 1 / 3 of the granules. After the aspiration is completed, the speed of the fixed hopper mixer is set to 12 rpm and mixed for 20 minutes to obtain a clear and antitussive composition.

[0076] Comparative Example 1 Preparation method of the clear and antitussive composition

[0077] The difference between this comparative example and Example 1 is that the density of concentration in step (2) is different, and the extract is not dried; and the specific steps of step (3) and step (4) are different.

[0078] The specific preparation method is:

[0079] (1) Add 3 times the amount of water to 108g of mint, 108g of fructus aurantii, and 144g of dried orange peel, and distill to extract 1.88g of volatile oil;

[0080] (2) 144 g of white peony root is soaked in water for 4 hours, and then combined with 216 g of mulberry leaf, 108 g of fried bitter almond, 144 g of platycodon, 144 g of aster and 108 g of liquorice. The residue after the volatile oil extraction in step 1) is soaked in 10 times the amount of water for 30 min, and decocted twice, each time for 1 hour. The decoction is filtered through an 80-mesh sieve at the bottom of the pot, and the filtrate released is the first extract; the filtered residue is added with 8 times the amount of water again, and the same operation is performed, and the filtrate extracted is the second extract; the two extracts are combined and concentrated to a relative density of 1.10-1.15 (50° C.), and then passed through a 300-mesh sieve while hot, and then continued to be concentrated under reduced pressure to a relative density of 1.30-1.35 (50° C.), and the fluid extract is released, and filtered through a 300-mesh sieve while hot to obtain 350 g of extract;

[0081] (3) 567.4 g of sucrose was crushed with an 80-mesh grinder and added to a wet granulator with 283.7 g of dextrin. The stirring speed was set to 100 rpm and the chopping speed was set to 1000 rpm. The mixture was mixed for 300 s. 6 g of ethanol was added and stirred for 100 s. 50% of the extract was weighed and added. When the current reached 29 A after mixing for 30-80 s, the mixing was stopped. The inlet air temperature was set to 100° C. and the material temperature was dried at 80° C. When the material temperature reached 80° C., the material was dried for 10 minutes. The heating was stopped and the temperature was lowered. When the material temperature reached 50° C. or below, the material was discharged and crushed with a 60-mesh grinder to obtain the extract powder.

[0082] (4) Add the extract powder to the wet mixing granulator, set the stirring blade speed to 100 rpm, the chopping speed to 1000 rpm, mix for 300 seconds, add 21 g of ethanol, stir for 100 seconds, weigh 50% of the extract and add, mix for 40 seconds, chop for 20 seconds, stop mixing when the current reaches 73A, discharge, granulate the soft material through 20 mesh, and dry the wet granules through boiling, set the inlet air temperature to 90°C and the material temperature to 75°C. When the material temperature reaches 75°C, continue drying for 10 minutes, stop heating and cooling, and discharge when the material temperature reaches below 50°C. Screen the granules with 14 mesh / 60 mesh, and granule that does not pass 14 mesh through 12 mesh and then select the granules to obtain the selected granules and fine powder that passes the sieve;

[0083] (5) adding 1 times the amount of β-cyclodextrin of the volatile oil and 4 times the amount of the fine powder obtained in step (4) into a high-efficiency mixing granulator, setting the stirring frequency to 50 Hz, the flying cutter to run at high speed, stirring for 4 minutes, pouring the volatile oil obtained in step (1), stirring for 2 minutes, and passing the discharged material through a 14-mesh sieve to obtain an inclusion compound;

[0084] (6) The inclusion compound obtained in step (5) and the selected granules obtained in step (4) are aspirated into a 3000 L total mixing barrel three times, with each aspirating amount being 1 / 3 of the inclusion compound and 1 / 3 of the granules. After the aspiration is completed, the speed of the fixed hopper mixer is set to 8 rpm and mixed for 20 minutes to obtain a clear and antitussive composition.

[0085] Comparative Example 2 Preparation method of CN1242770C Qingxuan cough relieving granules

[0086] Weigh each raw material according to the weight ratio:

[0087] 216g mulberry leaves, 108g mint, 108g bitter almond, 144g platycodon, 144g white peony root, 108g fructus aurantii, 144g tangerine peel, 144g aster, and 108g licorice.

[0088] First, the peppermint, tangerine peel and fructus aurantii in the above raw materials are steam distilled to extract volatile oil, and the volatile oil is liquid-liquid inclusion complexed with β-cyclodextrin (5 g of β-cyclodextrin is added to each ml of oil at 30° C. and a stirring speed of 100 rpm for 4 hours) to obtain inclusion compound A. The distilled water and the residues are decocted twice with 10 times the amount of water together with the other six medicinal materials, each time for 1 hour, the decoctions are combined, filtered, and the filtrate is concentrated to a relative density of 1.35 (50° C.), dried at low temperature under reduced pressure, and ground to obtain a dry paste B. 1 part of the dry paste powder, 2 parts of sucrose, 1 part of dextrin and an appropriate amount of ethanol are taken to prepare granules, which are dried, and the inclusion compound A is added, mixed, and granulated.

[0089] Comparative Example 3 Preparation method of the clear and antitussive composition

[0090] The difference between this comparative example and Example 1 is that: the density of concentration in step (2) is different; the amount of auxiliary materials and the addition of ethanol in step (3) are different; and the parameters included in step (5) are different.

[0091] (1) Add 3 times the amount of water to 108g of mint, 108g of fructus aurantii, and 144g of dried orange peel, and distill to extract 1.18g of volatile oil;

[0092] (2) 144 g of white peony root slices were soaked in water for 4 hours, and then combined with 216 g of mulberry leaves, 108 g of fried bitter almonds, 144 g of platycodon grandiflorum, 144 g of aster, and 108 g of liquorice. The residues after the volatile oil extraction in step (1) were soaked in 8 times the amount of water for 30 minutes; the mixture was decocted twice, the first decoction was 1 hour, and the decoction was filtered through an 80-mesh sieve at the bottom of the tank, and the filtrate released was the first extract; the filtered residues were added with 8 times the amount of water again, and the same operation was performed, and the filtrate extracted was the second extract; the two extracts were combined and concentrated to a relative density of 1.10-1.15 (measured at 50°C), and then passed through a 300-mesh sieve while hot, and continued to be concentrated under reduced pressure to a relative density of 1.30-1.35 (measured at 50°C), and then filtered through a 300-mesh sieve while hot to obtain an extract; the extract obtained in (2) was dried using a vacuum dryer to obtain 300 g of extract powder;

[0093] (3) 466.6 g of sucrose was crushed through 80 mesh, and 300 g of extract powder was crushed through 80 mesh; 466.6 g of sucrose powder, 233.3 g of dextrin, and 300 g of extract powder were sucked into a wet mixing granulator, and after mixing, 60 g of 80% ethanol was added, and after stirring evenly, 75 g of 80% ethanol was added and stirred; the soft material was sieved through a 20-mesh sieve for granulation; the wet granules were sucked into a boiling dryer, and when the material temperature reached 75°C, the drying was continued for 10 minutes, the heating was stopped, and the temperature began to be lowered. When the material temperature reached below 50°C, the material was discharged; the dried granules were selected, and the granulation screen mesh number was 14 mesh / 60 mesh. The granules that did not pass the 14-mesh screen were re-granulated through a 12-mesh screen and then selected to obtain selected granules;

[0094] (4) adding 0.5 times the amount of β-cyclodextrin as the volatile oil and 5 times the amount of the volatile oil as the fine powder obtained in step (3) to a high-efficiency mixing granulator, stirring for 4 minutes, pouring in the volatile oil obtained in step (1), stirring for 2 minutes, and passing the discharged material through a 14-mesh sieve to obtain an inclusion compound;

[0095] (5) The inclusion compound obtained in step (4) and the selected granules obtained in step (3) are aspirated into a 3000 L total mixing barrel three times, with each aspirating amount being 1 / 3 of the inclusion compound and 1 / 3 of the granules. After the aspiration is completed, the speed of the fixed hopper mixer is set to 8 rpm and mixed for 20 minutes to obtain a clear and antitussive composition.

[0096] Example 4 Determination of the effective ingredients of the Qingxuan cough-relieving composition prepared

[0097] The content was determined according to the high performance liquid chromatography method (General Rule 0512) in the national pharmacopoeia standard.

[0098] The results are shown in Table 1.

[0099] Table 1 Content of paeoniflorin and hesperidin (unit: mg)

[0100] sample Paeoniflorin content Hesperidin content Example 1 21.7 14.7 Example 2 21.2 14.9 Example 3 20.9 14.6 Comparative Example 1 13.0 11.5 Comparative Example 2 10.7 8.5 Comparative Example 3 18.5 13.8

[0101] Results of long-term stability study of the Qingxuan cough-relieving composition prepared in Example 5

[0102] Take this product and place it at a temperature of 25℃±2℃ and a relative humidity of 60%±5%, and take samples for testing at 0, 3, 6, 9, 12 and 18 months respectively.

[0103] The content was determined according to the high performance liquid chromatography method (General Rule 0512) in the national pharmacopoeia standard.

[0104] The results are shown in Table 2.

[0105] Table 2 Content of paeoniflorin and hesperidin (unit: mg)

[0106]

[0107] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing a cough-clearing composition, characterized in that: The following steps are involved: (1) steam distilling peppermint, fructus aurantii, and tangerine peel to obtain volatile oil; (2) extracting white peony root, mulberry leaf, fried bitter almond, platycodon grandiflorum, aster, liquorice and the residue after distillation in step (1) with water, and concentrating and drying the water extract under reduced pressure to obtain extract powder; (3) mixing the extract powder with sucrose and dextrin, granulating, screening and granulating to obtain the selected granules and the fine powder passing through the sieve; (4) mixing β-cyclodextrin and the fine powder obtained in step (3) and stirring, then adding the volatile oil obtained in step (1) and stirring again, and sieving the discharged material to obtain an inclusion compound; (5) Mixing the inclusion compound obtained in step (4) and the selected particles obtained in step (3) to obtain.

2. The preparation method according to claim 1, characterized in that The following steps are involved: (1) steam distilling peppermint, fructus aurantii, and tangerine peel to obtain volatile oil; (2) soaking white peony root in water, and continuing to extract with mulberry leaf, fried bitter almond, platycodon, aster, liquorice and the residue after distillation in step (1), separating the solid and liquid, concentrating and drying the filtrate, and crushing to obtain extract powder; (3) crushing sucrose and the extract powder obtained in (2), mixing the extract powder with sucrose and dextrin, adding ethanol, stirring, granulating to obtain wet granules, drying, cooling, discharging, screening and granulating to obtain selected granules and fine powder passing through a sieve; (4) mixing β-cyclodextrin and the fine powder obtained in step (3) and stirring, adding the volatile oil obtained in step (1) and stirring again, and sieving the discharged material to obtain an inclusion compound; (5) Mixing the inclusion compound obtained in step (4) and the selected particles obtained in step (3) to obtain.

3. The preparation method according to claim 2, characterized in that: In step (1), the mass of water added is 1.2-12 times the mass of mint, fructus aurantii and tangerine peel, preferably 1.6-8 times, and more preferably 2-4 times.

4. The preparation method according to claim 2, characterized in that: In step (2), the mass of water added is 4.8-24 times, preferably 6.4-16 times, and more preferably 8-12 times, of the total mass of white peony root, mulberry leaf, fried bitter almond, platycodon, aster, licorice and distilled medicinal residues; the number of water extractions is 1-3 times, preferably 2 times; the water extraction time is 0.6-3h, preferably 0.8-2h, and more preferably 1h; the concentration is reduced pressure concentration, and the reduced pressure concentration is concentrated to a relative density of 1.0-1.35, preferably 1.05-1.20, and more preferably 1.10-1.25; the number of reduced pressure concentrations is 1-3 times, preferably 2 times; preferably, when the number of reduced pressure concentrations is 2 times, the first concentration is concentrated to a relative density of 1.03-1.

09.

5. The preparation method according to claim 2, characterized in that: The amount of sucrose and dextrin used in step (3) is 1.5-3 times the mass of the extract powder, preferably 1.8-3 times, and more preferably 2-3 times; the mass ratio of sucrose to dextrin is 1-3:1, preferably 1.5-2.5:1, and more preferably 2:

1.

6. The preparation method according to claim 2, characterized in that: The number of times that ethanol is added in step (3) is 1-3 times, preferably 2 times; preferably, when ethanol is added 2 times, the concentration of the first ethanol addition is 95v / v%, and the mass of the added ethanol is 2.5-30% of the total weight of the extract powder, sucrose and dextrin; preferably 5-20%; more preferably 7.5-10%; the concentration of the second ethanol addition is 25%-75%, preferably 30%-70%, more preferably 44%-65%; the mass of the second ethanol addition is 6-10% of the total weight of the extract powder, sucrose and dextrin, preferably 6.5-8%, more preferably 7.3%-7.9%.

7. The preparation method according to claim 1, characterized in that: In step (4), the mass ratio of the volatile oil to β-cyclodextrin is 1:0.6-1.4, preferably 1:0.8-1.2; the mass ratio of the volatile oil to the fine powder obtained in step (4) is 1:1.2-54, preferably 1:1.6-18, and more preferably 1:2-6.

8. The preparation method according to claim 2, characterized in that: The following steps are involved: (1) adding 3 times the amount of water to mint, fructus aurantii, and tangerine peel, and performing distillation extraction to obtain volatile oil; (2) soaking white peony root in water, combining it with mulberry leaf, fried bitter almond, platycodon, aster and licorice; soaking the residue after volatile oil extraction in step (1) in 10 times amount of water for 30 minutes, decocting twice, each time for 1 hour, filtering the decoction to obtain the first extract; adding 8 times amount of water to the residue after filtration, and operating in the same way, and the filtrate obtained is the second extract; combining and concentrating the two extracts to a relative density of 1.03-1.09, sieving while hot, continuing to reduce pressure and concentrate to a relative density of 1.15-1.20, filtering while hot to obtain an extract; drying the extract to obtain an extract powder; (3) crushing sucrose, mixing sucrose powder, dextrin and extract powder, adding 95% ethanol, stirring evenly, and then adding 55% ethanol and stirring; making wet granules from the soft material, and drying; selecting the dried granules to obtain selected granules and fine powder passing through a sieve; (4) sequentially mixing 1 times the amount of β-cyclodextrin as the volatile oil and 4 times the amount of the fine powder obtained in step (3), stirring for 4 minutes, pouring in the volatile oil obtained in step (1), stirring for 2 minutes, and filtering the discharged material through a 14-mesh sieve to obtain an inclusion compound; (5) The inclusion compound obtained in step (4) and the selected granules obtained in step (3) are mixed three times, with each mixing amount being 1 / 3 of the inclusion compound and 1 / 3 of the granules.

9. A cough-clearing composition, characterized in that: Prepared by the preparation method according to any one of claims 1 to 8.

10. The cough-clearing and cough-relieving composition according to claim 9, characterized in that: In terms of weight, the proportion of raw materials is 108 parts of mint, 54-162 parts of Citrus aurantium, 72-216 parts of dried tangerine peel, 72-216 parts of white peony root, 108-324 parts of mulberry leaf, 54-162 parts of fried bitter almond, 72-216 parts of Platycodon grandiflorum, 72-216 parts of Aster tataricus and 54-162 parts of licorice; preferably, 108 parts of mint, 108 parts of Citrus aurantium, 144 parts of dried tangerine peel, 144 parts of white peony root, 216 parts of mulberry leaf, 108 parts of fried bitter almond, 144 parts of Platycodon grandiflorum, 144 parts of Aster tataricus and 108 parts of licorice.

11. Use of the preparation method according to any one of claims 1 to 8 or the Qingxuan Antitussive Composition according to claim 9 in preparing medicine for treating exogenous wind-heat cough.

12. A cough-relieving medicine, characterized in that: The preparation method according to any one of claims 1 to 8 or the Qingxuan antitussive composition according to claim 9 is prepared. Preferably, the Qingxuan antitussive drug is in the form of granules, tablets or capsules.

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